DNA ploidy and S-phase fraction as predictive factors of response and outcome following neoadjuvant methotrexate, vinblastine, epirubicin and cisplatin (M-VEC) chemotherapy for invasive bladder cancer.

OBJECTIVE: To investigate the value of DNA ploidy and S-phase fraction (SPF) as factors that could predict response and outcome of invasive transitional cell carcinoma (TCC) of the bladder to neoadjuvant methotrexate, vinblastine, epirubicin and cisplatin (MVEC) chemotherapy. MATERIALS AND METHODS: Twenty-four patients with localized invasive TCC of the bladder (stages T3 to T4a, NoMo) were treated with neoadjuvant MVEC chemotherapy. DNA flow cytometry was performed in paraffin-embedded tissue obtained by transurethral resection before chemotherapy. Radical cystectomy specimens were utilized for complete pathologic staging. The tumors were subdivided into high- and low-SPF tumors according to their SPF value. DNA ploidy status was evaluated into two groups (diploidy and nondiploidy). RESULTS: DNA ploidy was not correlated to the response to chemotherapy (p = 0.67), and overall or disease-free survival (p = 0.27 and p = 0.69, respectively). Major response (pathologic complete response and partial response) was more often found in the high SPF group than among tumors with low SPF (p = 0.02). High SPF tumors were significantly associated with increased overall and disease-free survival (p = 0.0056 and p = 0.0059, respectively). CONCLUSION: A high SPF, but not DNA ploidy, may be helpful to identify patient likely to respond and survive longer following neoadjuvant MVEC chemotherapy in the treatment of invasive bladder cancer.

A nonrefluxing, serous lined extramural tunnel for ureteroileal anastomosis in ileal conduit urinary diversion: first clinical experience in 10 patients.

PURPOSE: We report the surgical technique and functional outcome of a new application for serous lined, anti-refluxing ureteroileal anastomosis in ileal conduit urinary diversion. Reflux prevention relies on the construction of a serous lined extramural ileal tunnel. MATERIALS AND METHODS: A 25 cm. distal ileal segment was isolated. The proximal 7 cm. of the ileal segment was folded and the 2 proximal 7 cm. segments were joined by seromuscular sutures. The antimesenteric borders of these 7 cm. segments were incised and the medial edges of each ureter were joined. A mesenteric window was opened at the level of ileal folding and the ureters were passed through it. They were inlaid within the trough and the conjoined ureteral end were anastomosed to the intestinal mucosa. The tunnel was then closed over the implanted ureters. The lateral limbs of the detubularized ileal segment were then joined. The technique was performed in 10 patients with a mean followup of 9.9 months (range 3 to 19). The patients were evaluated clinically and radiologically. RESULTS: None of the 10 patients had reflux on x-ray of the loop. One patient had previously undergone unilateral nephrectomy. Excretory urography showed a stabilized or improved upper tract in 18 renal units. Left ureterohydronephrosis was present in 1 renal unit because of ureteroileal stenosis. CONCLUSIONS: The initial clinical results of the serous lined extramural ileal tunnel technique for ureteroileal anastomosis in ileal conduit cases are promising. The technique appears effective and reliable.

P53, bcl-2 and bax immunoreactivity as predictors of response and outcome after chemotherapy for metastatic germ cell testicular tumours.

OBJECTIVE: To evaluate the roles of p53, bcl-2 and bax as determinants of chemosensitivity in testicular cancers and to assess whether immunohistochemical expression of these proteins in testicular germ cell tumours (GCTs) could be used to predict the outcome in patients with metastatic testicular GCTs. PATIENTS AND METHODS: Immunoreactivity for p53, bcl-2 and bax were examined in primary testicular tumours from 24 patients with metastatic GCTs who were treated with bleomycin, etoposide and cisplatin chemotherapy. All immunostaining results were scored for the appropriate percentage of positive tumour cells and relative immunostaining intensity (score range 0-15) and compared with the response of the patients to chemotherapy. RESULTS: Overall, 20 (83%), 13 (54%) and 24 of the 24 GCTs showed > or = 1% immunoreactivity with p53, bcl-2 and bax, respectively. Only the bax immunostaining intensity and score had statistically higher mean values in the nonseminoma than in seminoma GCTs (P = 0.047 and P = 0.027, respectively). Only p53 immunostaining intensity, percentage of p53 immunopositive cells and p53 staining score were sig-nificantly different among the response groups. The median survival after chemotherapy was 30.5 months; however, taking the median values of the immunostaining scores as threshold values for the survival analysis, none of the three proteins were associated with significant differences in survival. CONCLUSIONS: The incidence of p53 and bax immuno-reactivity in testicular GCTs is higher than that of bcl-2 immunoreactivity. However, only p53 immuno-reactivity could be used to predict the response to chemotherapy. P53, bcl-2 and bax scores were not significant prognostic factors for survival after chemotherapy.

Combined interferon alpha with levamisole in patients with metastatic renal cell carcinoma.

To evaluate the efficacy and toxicity of interferon alpha-2b (IFN-alpha2b) and levamisole treatment regimen in patients with metastatic renal cell carcinoma (RCC). Seventeen patients with metastatic RCC were treated using recombinant IFN-alpha2b at a dose of 10 MU/m2 body surface subcutaneously three times in a week, for 3 months, with levamisole 50 mg t.d.s orally on days 1-3 on alternate weeks. The mean follow-up period was 10.7 (range 2-23) months. We achieved 1 complete response (lasting for 12+ months) and 1 partial response (lasting for 15 months), for an objective response rate of 11.7%. A further 7 patients (41%) had a stabilization of disease. The overall toxicity was moderate, with mainly grade I or II side effects. Grade III toxicities reported among 3 patients including vomiting (2 patients) and anorexia (1 patient). There was no treatment related death. Although additions of levamisole to IFN-alpha do not result in any significant increase in treatment toxicity, the response rate appears to be no better than IFN-alpha monotherapy reported in the literature.

Palliative analgesic effect of Re-186 HEDP in various cancer patients with bone metastases.

UNLABELLED: The clinical picture of bone metastases is manifested by pain and loss of mechanical stability. Standard treatment options for bone metastases include external beam radiotherapy and the use of analgesics. Due to a large number of lesions in many patients, the use of radionuclide therapy with beta emitters may be preferable. Re-186 hydroxyethylidene diphosphonate (Re-186 HEDP) is one of the radiopharmaceuticals suitable for palliative treatment of metastatic bone pain. The aim of this study was to investigate palliative and side effects of Re-186 HEDP in patients with different types of cancers. MATERIAL & METHOD: Thirty one (17 male, 14 female) patients with various cancers (10 prostate, 10 breast, 4 rectum, 5 lung, 2 nasopharynx) and bone metastases were included in the study. Therapy was started with a fixed dose of 1295 MBq of Re-186 HEDP. If necessary, the same dose was repeated at least 3 times after an interval of 10-12 weeks; A total of 40 standard doses were given; 6 patients received repeated doses (3 doses in 3 patients, 2 doses in 3 patients). The patients with bone marrow suppression were excluded from the study. The pain relief was assessed the Eastern Cooperative Oncologic Group (ECOG) and the Karnofsky status index. All patients were evaluated with standard evaluation forms filled in daily for a maximum of 10 weeks. RESULTS: The mean response rate was 87.5% in patients with breast and prostate cancer, 75% in patients with rectum cancer and 20% in patients with lung cancer. The overall response rate was 67.5%. The palliation period varied between 6 and 10 weeks, with a mean of 8.1+/-1.3 weeks. The maximal palliation effect was observed between the 3rd and 7th weeks. No serious side effects were seen except mild hematologic toxicity. DISCUSSION & CONCLUSION: It is concluded that Re-186 HEDP is a highly effective agent in the palliation of metastatic bone pain in patients with prostate, breast and rectum cancer, but not effective in lung cancer. On the other hand, Re-186 seems to be a good alternative to Sr-89 because of its preferable physical characteristics (such as short half life and gamma energy emission), low side effect profile, early response and repeatability.

Influence of tumor stage, size, grade, vascular involvement, histological cell type and histological pattern on multifocality of renal cell carcinoma.

PURPOSE: We assessed the influence of clinical and pathological factors on multifocality of renal cell carcinoma. MATERIALS AND METHODS: Between June 1995 and September 1999 radical nephrectomy was performed in 71 men and 32 women with a mean age of 56.5 years. The 103 removed kidneys with renal cell carcinoma were sectioned at 3 mm. intervals and inspected microscopically for satellite carcinomas. We evaluated pathological stage, grade, cell type, histological pattern, vascular involvement, tumor size and the incidence of multifocality. To determine cell type we used several classification systems. RESULTS: The primary tumor was 2 to 20 cm. (mean plus or minus standard deviation 7.10 +/- 3.48). Overall satellite carcinomas were present in 22 of the 103 cases (21.4%). When the predominant lesion was 5 cm. or smaller, the incidence of multifocality was 19%. The incidence of multifocality was statistically higher in patients with stage pT3 than in those with stage pT1 or pT2 disease (p = 0.022). Multiple logistic regression analysis demonstrated that only primary tumor pathological stage was a significant predictor of renal cell carcinoma multifocality in stages T3 versus T1 and T3 versus T2 cancer (odds ratio 3.45, 95% confidence interval 1.15 to 10.39 and 5.75, 1.31 to 25.29, respectively). Other parameters, such as tumor size, grade, vascular invasion, cell type and histological pattern, did not correlate with multifocality. CONCLUSIONS: Our results imply that primary tumor stage is a significant factor for multifocal disease. Therefore, more precise preoperative staging of the primary lesion is required if nephron sparing surgery is indicated.

The prognostic value of peripheral blood lymphocyte subsets in patients with bladder carcinoma treated using neoadjuvant M-VEC chemotherapy.

OBJECTIVES: To assess the prognostic value of peripheral blood lymphocyte subsets in patients with bladder cancer who were treated with neoadjuvant chemotherapy. PATIENTS, SUBJECTS AND METHODS: Thirty patients with a histological diagnosis of invasive bladder transitional cell carcinoma and 30 age-matched controls with no evidence of cancer and immunological disorders were evaluated. Peripheral blood samples were assessed in both groups using monoclonal antibodies. Patients with bladder cancer who achieved complete or partial responses and those who had progression of the disease after systemic chemotherapy with methotrexate, vinblastine, epirubicin and cisplatin were compared according to the pretreatment values of the peripheral blood lymphocyte subsets. RESULTS: There were no significant differences in B lymphocyte levels between the groups. In patients with bladder cancer, the percentages of T lymphocytes (P<0.01), natural killer (NK) cells (P<0.05) and the CD4+/CD8+ ratio (P<0.05) were significantly lower than in the control group. In patients who responded to the chemotherapy regimen, the pretreatment values of T lymphocytes (P<0.001), the CD4+/CD8+ ratio (P<0.01) and NK cell levels (P<0.01) were significantly higher than in the patients who did not. CONCLUSION: In patients with invasive bladder carcinoma, cell-mediated immunity may have a role in the resistance to this malignancy and in these patients the pretreatment levels of T lymphocyte subsets may be an indicator of the potential response to chemotherapy.

Does the position of the patient affect the presence and/or degree of reflux in an ileal conduit urinary diversion?

OBJECTIVE: To assess the effect of patient position (supine, sitting or standing) on ileo-ureteric reflux in patients with an ileal conduit urinary diversion, in whom such reflux is normally detected when they are supine during a retrograde loopogram. PATIENTS AND METHODS: The study included 10 patients with an ileal conduit as a primary urinary diversion; a loopogram was obtained with the patient upright or supine and a further film taken with the patient supine but at 45 degrees to the ground. RESULTS: When supine, free ileo-ureteric reflux occurred into both ureterorenal units in eight patients. The remaining two patients, who had previously undergone unilateral nephrectomy, also had reflux into their existing renal units. Of the 18 units, 15 had grade III and three had grade IV reflux. In the upright and 45 degrees position, reflux still occurred in al ureterorenal units. The patient's position did not affect the degree of reflux in 16 units, but in one unit with grade IV reflux and another with grade III reflux, the reflux was one grade less severe. CONCLUSIONS: Ileo-ureteric reflux is common after ileal conduit diversion and may contribute to the likelihood of renal deterioration. The presence and/or degree of reflux is generally not affected by the position of the patient.

Management of ureterointestinal obstruction and extensive loss of the ureter by creating a pedicle tube graft from the orthotopic neobladder.

We report a case of ureterointestinal obstruction and extensive loss of the ureter following radical cystectomy and orthotopic bladder replacement. The patient was successfully treated by creating a pedicle tube graft from the orthotopic Mainz pouch.

Concurrent occurrence of three neoplasms including non-Hodgkin's lymphoma, renal cell carcinoma and leiomyoma in the same kidney.

A 53-year-old man with triple renal neoplasms in his left kidney presented. He was initially diagnosed intermediate grade non-Hodgkin's lymphoma (NHL) which involved gastrointestinal tract, left kidney, liver and pancreas. He underwent left nefrectomy because of a persistent renal mass after the completion of chemotherapy. The large renal mass revealed a renal cell carcinoma (RCC). Additionally, multiple small nodules of non-Hodgkin's lymphoma and a solitary leiomyoma were observed.

Evaluation of serum arginase activity in benign prostatic hypertrophy and prostatic cancer.

Activities of arginase, prostatic acid phosphatase (PAP) and prostate specific antigen (PSA) were determined in sera of healthy male controls, benign prostatic hypertrophy (BPH) and prostatic cancer patients. Serum arginase activity in the cancer group (22.8+/-11.6 U/l) was significantly lower than in both the control (33.64+/-16.19 U/l) and the BPH group (58.8+/-11.6 U/l) (p<0.001, respectively), while the BPH group had significantly higher levels compared to the controls (p<0.05). However, serum arginase levels in all groups had no statistically significant correlation with PAP and PSA. Serum arginase activity correlated inversely with the Gleason grades. These results suggest that serum arginase assay may be used for the pretreatment evaluation of patients with prostatic diseases.

Analysis of the peripheral blood lymphocyte subsets in patients with bladder carcinoma.

OBJECTIVES: To evaluate the immune system of patients with bladder transitional cell carcinoma (TCC) by using peripheral blood lymphocyte subsets and to further compare the relationship between these subsets with respect to tumor stage and grade (superficial versus invasive and low versus high grade). METHODS: Thirty patients with superficial TCC of the bladder, 30 patients with invasive TCC of the bladder, and 30 age- and sex-matched control subjects without any malignancy or immunologic abnormality were included in this study. The peripheral blood lymphocyte subset analysis was performed in all patients before any treatment was performed. RESULTS: All lymphocyte subset values of patients with invasive bladder cancer, except B cell value, were significantly lower (P < 0.01) than the values of the control group. There were no significant differences between the lymphocyte subset values of patients with superficial bladder cancer and those of control subjects. The comparison of the lymphocyte subset values of the patients with superficial versus invasive bladder carcinoma revealed that in patients with invasive bladder carcinoma, the numbers of T and natural killer (NK) cells were significantly lower (P < 0.05) than those of patients with superficial bladder carcinoma. Patients with high-grade tumors had significantly fewer (P < 0.05) T and NK cells than patients with low-grade tumors. CONCLUSIONS: Our results indicate that analysis of mean NK and T cell values and the mean ratio of CD4+/CD8+ cells in peripheral blood might be a useful adjunct for the clinical evaluation of patients with bladder cancer.

Activity of the enzymes participating in purine metabolism of cancerous and noncancerous human kidney tissues.

In this study, activity of some of the key enzymes participating in purine metabolism was measured in cancerous and noncancerous human kidney tissues from 18 patients with renal cell carcinoma. Twelve cancerous tissues were at stage T1-T2 and 6 tissues were at stage T3-T4. Adenosine deaminase (ADA) and guanase (GUA) activity was increased and xanthine oxidase (XO) activity decreased in cancerous tissues compared to noncancerous ones. No difference was, however, found between 5'-Nucleotidase (5'-NT) activity of the tissues. There were also no statistically meaningful differences between the enzyme activities of the cancerous tissues at stage T1-2 and T3-4. Results suggest that the changes observed in the activity of the enzymes participating in purine metabolism result from accelerated DNA turnover in the cancerous tissues and cells, and these changes might provide selective advantage, possibly by causing acceleration of salvage pathway activity, to the cancer cells to grow and develop more rapidly.

Activities of superoxide dismutase and glutathione peroxidase enzymes in cancerous and non-cancerous human kidney tissues.

The activities of superoxide dismutases (total, cytoplasmic and mitochondrial) and glutathione peroxidase were measured in 10 cancerous and 10 non-cancerous adjacent human kidney tissues. Total (T-SOD) and cytoplasmic (Cu, Zn-SOD) superoxide dismutase and glutathione peroxidase (GSH-Px) activities were found lower in cancerous tissues compared with those of non-cancerous ones. However, no difference was found between the mitochondrial (Mn-SOD) superoxide dismutase activities of the tissues. Similarly, no differences were observed between the enzyme activity values of the tissues at stage I-II and III-IV renal cancer. In correlation analysis the positive relation found between Cu, Zn-SOD and GSH-Px enzymes in the non-cancerous tissues was found to be absent in the cancerous ones. The results suggest that enzymatic free radical defense mechanism is significantly reduced in the cancerous human kidney tissues due to depressed Cu, Zn-SOD and GSH-Px activities.

Evaluation of urinary glycosaminoglycan excretion in patients with renal cell carcinoma.

OBJECTIVE: To evaluate a possible correlation between the urinary excretion of glycosaminoglycans (GAGs) and tumor stage and size in renal cell cancer (RCC), a prospective controlled study was performed. METHODS: 34 patients (13 females, 21 males) with clinically and histologically proven RCC were included in the study. Following the staging procedures of RCC in each patient nephrectomy was performed; subsequently the size of the tumor (length and width) was calculated using nephrectomy material. Urinary GAG excretion was determined using a previously described method. RESULTS: Urinary GAG excretion was found to be increased in RCC patients, with a strong relation to the size of the tumor. Patients with relatively larger tumor masses seemed to excrete higher amounts of GAGs in urine (r = 0.8235; p < 0.001). In contrast, we were not able to show any significant difference in urinary GAG excretion with respect to tumor stage (f = 5.92; p = 0.0068). Patients with multiple foci of RCC (n = 3) had relatively higher rates of GAG excretion than patients with same-size single-tumor masses. CONCLUSIONS: Although our results revealed GAG excretion in RCC patients as a possibly useful marker with respect to tumor size, no correlation to the stage of RCC was observed. Further investigation using larger series of patients and other definitive parameters is certainly needed in order to provide more reliable data, before considering urinary GAG excretion as a useful marker.

Evaluation and surgical treatment of patients with penile curvature.

In patients with adult penile curvatures the aim of treatment is to have a penis straight enough and firm enough to allow satisfactory sexual function. Several operative approaches have been used to correct this condition. Herein, we describe our experience with the evaluation and surgical treatment of 37 patients with penile curvature. When we have decided on surgery, we either preferred to elongate the ventral corpora cavernosa by interposition of a piece of dura mater (2 patients) or in most cases (the remaining 35 patients) only excised wedges of tunica albuginea at the arcs of the maximum curvature located with artificial erection (Nesbit's operation). In conclusion, our results showed that Nesbit's operation is a versatile procedure that proved to be useful for correction of penile curvatures in patients with Peyronie's disease. However, further studies and clinical trials are needed to determine if the dura mater is an alternative in the treatment of penile curvatures due to congenital aetiology.

Ultrastructual changes of corpora cavernosa in vascular erectile dysfunction.

Corpora cavernosa of 4 impotent patients with arterial pathology and 6 with venous insufficiency were studied by electron microscopy. The findings in all of the smooth muscle samples were the following: pronounced thickening of the basal lamina; marked reduction of contractile myofilaments and electron dense bodies; finger-like cytoplasmic projections; increase in mitochondria with swelling and aggregation; huge protrusions of nuclear membrane into the cytoplasm; increased proportion of interstitial matrix to smooth muscle cells. These were more marked in the dark than in the light cells, which was considered as the beginning of degeneration. Another finding was degenerative changes in the endothelial cell lining of the sinusoids, especially denudation, fragmentation and marked thickening of the basal lamina. Severity of the symptoms did not change in any of the patients with different pathologies. So, we can assume that the pathological alterations may be due to chronic penile vascular insufficiency or vice versa.

Evaluation of ischemia after ESWL: detection of free oxygen radical scavenger enzymes in renal parenchyma subjected to high-energy shock waves.

To evaluate the degree of ischemic formation at the tissue level after high-energy shock wave (HESW) application in a time- and dose-dependent manner, an experimental study in rabbits was performed. Following varying numbers of HESWs (1,000-2,000-3,000 shock waves) under fluoroscopic localization, treated kidneys were removed, by assessing tissue concentrations of two different free-radical scavenger enzymes (superoxide dismutase and catalase) the degree of formation of free oxygen radicals (i.e. ischemia) was evaluated. Evaluation of our results showed a statistically significant (p < 0.05) decrease in tissue scavenger enzyme levels (i.e. formation of free oxygen radicals) after 24 h following HESW application. However, results obtained 7 days after ESWL demonstrated disappearance of ischemia with normalization of tissue enzyme levels (p > 0.05).

Clinical experience with inflatable and malleable penile implants in 104 patients.

Penile prosthesis was implanted for erectile impotence of mainly organic origin in 104 patients. The AMS Dynaflex penile prosthesis was inserted in 39 cases, the AMS Malleable 600 prosthesis in 61 and the AMS Ultrex Plus prosthesis in 4. In 1 patient receiving a malleable prosthesis both rods had to be removed owing to erosion into the urethra and reimplantation was performed at the same operation. Only 1 patient who underwent implantation of the Dynaflex device had mechanical failure that necessitated surgical revision. After implantation of the new prosthesis both patients had satisfactory intercourse. One Dynaflex penile prosthesis, implanted into a juvenile-onset diabetic, became infected and required removal. Another complication was secondary to spontaneous erosion (noninfected) in 1 patient with malleable prosthesis who suffered loss of only one rod and who is still satisfied with the result. The overall complication rate in our series has been approximately 4%. The rest of the patients report satisfaction with the ability to move the penis voluntarily permitting normal sexual activities as well as normal appearance in the flaccid position. According to our experience, careful preoperative assessment from the views of both patient and device selection along with patient education, and strictly obeying the rules of sterility during implantation and applying systemic and local antimicrobial prophylaxis are essential in obtaining a successful result in prosthesis implantation for the individual patient.